This project intends to analyze the effects of antitumor agents on an established human colon carcinoma cell line in order to provide useful information relevant to the rational design of chemo- and radio-therapeutic clinical trials. Cell killing, defined as the inability to form colonies, will be studied after exposure to various drug concentrations or radiation doses at different time schedules. Cell cycle stage sensitivity will be investigated by treating synchronized cells. Effects on cell progression delay will be studied to define synchronizing agents. Cumulative effects of fractionated doses will be defined to estimate cell recovery. Therapeutic gain will be investigated by combination of drugs given simultaneously or sequentially. Methods will be developed to study the response of resting phase populations by the use of plateau phase cultures and multicellular spheroids. Other studies will be concerned with the kinetics of synthesis and release of CEA, their relation to cell cycle phase and the possible modifications induced by antitumor agents. A pilot study will be conducted to demonstrate the presence of a tumor-associated antigen on these cultured cells. Successful results lead to various studies concerning the epidemiology and mechanisms of the immune response in colon carcinoma and of changes in the expression of the tumor antigen induced by antitumor agents.